Drosophila Kruppel homolog 1 represses lipolysis through interaction with dFOXO

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2017-11-27
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Kang, Ping
Chang, Kai
Liu, Ying
Bouska, Mark
Birnbaum, Allison
Karashchuk, Galina
Thakore, Rachel
Zheng, Wenjing
Post, Stephanie
Brent, Colin S.
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Abstract
Transcriptional coordination is a vital process contributing to metabolic homeostasis. As one of the key nodes in the metabolic network, the forkhead transcription factor FOXO has been shown to interact with diverse transcription co-factors and integrate signals from multiple pathways to control metabolism, oxidative stress response, and cell cycle. Recently, insulin/FOXO signaling has been implicated in the regulation of insect development via the interaction with insect hormones, such as ecdysone and juvenile hormone. In this study, we identified an interaction between Drosophila FOXO (dFOXO) and the zinc finger transcription factor Kruppel homolog 1 (Kr-h1), one of the key players in juvenile hormone signaling. We found that Kr-h1 mutants show delayed larval development and altered lipid metabolism, in particular induced lipolysis upon starvation. Notably, Kr-h1 physically and genetically interacts with dFOXO in vitro and in vivo to regulate the transcriptional activation of insulin receptor (InR) and adipose lipase brummer (bmm). The transcriptional co-regulation by Kr-h1 and dFOXO may represent a broad mechanism by which Kruppel-like factors integrate with insulin signaling to maintain metabolic homeostasis and coordinate organism growth.
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This article is published as Kang, P., Chang, K., Liu, Y. et al. Drosophila Kruppel homolog 1 represses lipolysis through interaction with dFOXO. Sci Rep 7, 16369 (2017). https://doi.org/10.1038/s41598-017-16638-1. Works produced by employees of the U.S. Government as part of their official duties are not copyrighted within the U.S. The content of this document is not copyrighted.
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